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Bone Induction by Human Bone Morphogenetic Protein Gene Transfer Using Vectors

Research Project

Project/Area Number 15390612
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Surgical dentistry
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

BESSHO Kazuhisa  Kyoto University, Oral and Maxillofacial Surgery, Assistant Professor, 医学研究科, 助手 (90229138)

Co-Investigator(Kenkyū-buntansha) OKUBO Yasunori  Kyoto University, Oral and Maxillofacial Surgery, Assistant Professor, 医学研究科, 助手 (50378618)
IIZUKA Tadahiko  Kyoto University, Oral and Maxillofacial Surgery, Professor, 医学研究科, 教授 (80026921)
吉田 和也  京都大学, 医学研究科, 助手 (90263087)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 2004: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2003: ¥10,900,000 (Direct Cost: ¥10,900,000)
Keywordsbone morphogenetic protein / cytokine / recombinant / Escherichia Coli / plasmid / electroporation / bone induction / gene transfer
Research Abstract

Bone morphogenetic protein(BMP) gene transfer using BMP-expressing vectors is the original method to force a host's own cells to make BMP ; the development of this process greatly altered the ideas of then existing BMP research. The method utilizing an adenoviral vector had good gene transfer efficiency and it was an effective technique, but the problem of immunoreaction was left to the adenovirus vector. To overcome this problem, while having the general application of an immunosuppressant and partial application, the use of a biomaterial (atelopeptide collagen) to mask the immune response etc. was examined. As the immune system could be transiently controlled by the above methods, we believed that the adenoviral vector can be applied to clinical use.
Useful results were obtained in an examination of the general or partial application of an immunosuppressant on bone induction by BMP gene transfer using the BME-expressing adenoviral vector. The application of biomaterial (atelopeptide collagen) to mask the immune response succeeded in obtaining local immune suppression. Our results suggested that gene therapy with the BMP-2-expressing adenoviral vector could be performed under transient immunosuppression, with general or local application of an immunosuppressant and effective masking of the host immune response ; thus being useful for bone reconstruction.
Moreover, we paid attention to a BMP-expressing plasmid vector that could be safely used in vivo, and examined gene transfer methods using the BMP-expressing plasmid vector with electroporation ; obtaining useful results. This method should soon become a very useful clinical tool for bone reconstruction, and should also contribute to the development of new treatment methods.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (22 results)

All 2004 2003 Other

All Journal Article (15 results) Book (1 results) Publications (6 results)

  • [Journal Article] Effect of Phosphorin on rhBMP-2-induced Bone Formation.2004

    • Author(s)
      Takashi Saito, Fumito Kobayashi, et al.
    • Journal Title

      Archives of Oral Biology 49

      Pages: 239-243

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Acceleration of Human Recombinant Bone Morphogenetic Protein-2 on Differentiation of Human Pulp Cells into Odontoblasts.2004

    • Author(s)
      Takashi Saito, Masafumi Ogawa, et al.
    • Journal Title

      Journal of Endodontics 30

      Pages: 205-208

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Isolation and Characterization of a Mesenchymal Cell Line That Differentiates into Osteoblasts in Response to BMP-2 from Calvariae of GFP Transgenic Mice.2004

    • Author(s)
      Aki Kadowaki, Tomoo Tsukazaki, et al.
    • Journal Title

      Bone 34

      Pages: 993-1003

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Osteoinduction by Bone Morphogenetic Protein 2-Expressing Adenoviral Vector : Application of Biomaterial to Mask the Host Immune Response.2004

    • Author(s)
      Junya Sonobe, Yasunori Okubo, et al.
    • Journal Title

      Human Gene Therapy 15

      Pages: 659-668

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Isolation and Characterization of a Mesenchymal Cell Line That Differentiates into Osteoblasts in Response to BMP-2 from Calvariae of GEP Transgentc Mice.2004

    • Author(s)
      Aki Kadowaki, Tomoo Tsukazaki, et al.
    • Journal Title

      Bone 34

      Pages: 993-1003

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 喫煙の歯科インプラント治療に対する影響-歯科インプラント周囲骨形成へのニコチンの経時的影響に関する研究-2004

    • Author(s)
      別所和久, 前田潤一郎, 他
    • Journal Title

      喫煙科学研究財団研究年報 平成15年度

      Pages: 239-243

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Over Expression of Bone Morphogenetic Protein-3b (BMP-3b) Using an Adenoviral Vector Promote the Osteoblastic Differentiation in C2C12 Cells and Augment the Bone Formation Induced by Bone Morphogenetic Protein-2 (BMP-2) in Rats.2003

    • Author(s)
      Shinji Kaihara, Kazuhisa Bessho, et al.
    • Journal Title

      Life Science 72

      Pages: 1683-1693

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Preclinical Study of Recombinant Human Bone Morphogenetic Protein-2 : Application of Hyperbaric Oxygenation during Bone Formation under unfavourable condition.2003

    • Author(s)
      Yasunori Okubo, Kazuhisa Bessho, et al.
    • Journal Title

      International Journal of Oral and Maxillofacial Surgery 32

      Pages: 313-317

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Ectopic Bone Formation by Human Bone Morphogenetic Protein-2 Gene Transfer to Skeletal Muscle Using Transcutaneous Electroporation.2003

    • Author(s)
      Mariko Kawai, Kazuhisa Bessho, et al.
    • Journal Title

      Human Gene Therapy 14

      Pages: 1547-1556

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] In Vivo Study on the Effect of Nicotine on Bone Formation.2003

    • Author(s)
      Kazuhisa Bessho, Jun-ichiro Maeda, et al.
    • Journal Title

      Oral Oncology 9

      Pages: 258-261

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Simple and Effective Osteoinductive Gene Therapy by Local Injection of a Bone Morphogenetic Protein-2-expressing Recombinant Adenoviral Vector and FK506 Mixture in Rats.2003

    • Author(s)
      Sinji Kaihara, Kazuhisa Bessho, et al.
    • Journal Title

      Gene Therapy 11

      Pages: 439-447

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Over Expression of Bone Morphogenetic Protein-3b(BMP-3b) Using an Adenoviral Vector Promote the Osteoblastic Differentiation in C2C12 Cells and Augment the Bone Formation Induced by Bone Morphogenetic Protein-2(BMP-2) in Rats.2003

    • Author(s)
      Shinji Kaihara, Kazuhisa Bessho, et al.
    • Journal Title

      Life Science 72

      Pages: 1683-1693

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Preclinical Study of Recombinant Human Bone Morphogenetic Protein-2 : Application of Hyperbaric Oxygenation during Bone Formation under unfavorable condition.2003

    • Author(s)
      Yasunori Okubo, Kazuhisa Bessho, et al.
    • Journal Title

      International Journal of Oral and Maxillofacial Surgery 32

      Pages: 313-317

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Osteoinduction by a Human Bone Morphogenetic Protein-2 Expressing Adenoviral Vector.2003

    • Author(s)
      Kazuhisa Bessho
    • Journal Title

      Recent Research Developments in Biophysics & Biochemistry(Research Signpost)

      Pages: 613-630

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] チタン製インプラント材からのチタンイオン溶出,BMP(骨形成因子)による骨再生2003

    • Author(s)
      別所和久, 飯塚忠彦
    • Journal Title

      バイオマテリアル-生体材料- 21

      Pages: 457-464

    • NAID

      50000357854

    • Related Report
      2004 Annual Research Report
  • [Book] Recent Research Developments in Biophysics & Biochemistry2003

    • Author(s)
      Kazuhisa Bessho
    • Total Pages
      1012
    • Publisher
      Research Signpost
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Publications] Shinji Kaihara, Kazuhisa Bessho, et al.: "Over Expression of Bone Morphogenetic Protein-3b (BMP-3b) Using an Adenoviral Vector Promote the Osteoblastic Differentiation in C2C12 Cells and Augment the Bone Formation Induced by Bone Morphogenetic Protein-2 (BMP-2) in Rats"Life Science. 72. 1683-1693 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yasunori Okubo, Kazuhisa Bessho, et al.: "Preclinical Study of Recombinant Human Bone Morphogenetic Protein-2 : Application of Hyperbaric Oxygenation during Bone Formation under unfavourable condition"International Journal of Oral and Maxillofacial Surgery. 32. 313-317 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Mariko Kawai, Kazuhisa Bessho, et al.: "Ectopic Bone Formation by Human Bone Morphogenetic Protein-2 Gene Transfer to Skeletal Muscle Using Transcutaneous Electroporation"Human Gene Therapy. 14. 1547-1556 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kazuhisa Bessho, Jun-ichiro Maeda, et al.: "In Vivo Study on the Effect of Nicotine on Bone Formation"Oral Oncology. 9. 258-261 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sinji Kaihara, Kazuhisa Bessho, et al.: "Simple and Effective Osteoinductive Gene Therapy by Local Injection of a Bone Morphogenetic Protein-2-expressing Recombinant Adenoviral Vector and FK506 Mixture in Rats"Gene Therapy. 11. 439-447 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 海原真治, 別所和久 他: "アテロコラーゲンスポンジ(TERUPLUG)を担体とする遺伝子組み換えヒト骨形成因子の骨誘導に関する研究 -アテロペプチドコラーゲン(Cellmatrix LA)を担体とした場合との比較-"日本口腔外科学会雑誌. 49. 241-245 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2021-12-10  

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